Carcinoma of the ovary kills more women in North America and Europe than all other gynecological malignancies combined. Worldwide, the incidence is estimated to include 190,000 new cases and 114,000 deaths annually. Despite advances in surgical approaches and chemotherapeutic agents, ovarian cancer has the third lowest survival rate out of 11 different organ categories. In the United States it is the fourth most frequent cause of cancer death among women. Of all females born in the United States, one of every 70 will develop ovarian cancer and one of every 100 will die from this disease. Unfortunately, the vast majority of patients are diagnosed at an advanced clinical stage where the average 5-year survival is 30%. Fortuitous detection of early stage tumors is associated with a substantial increased 5-year survival (>95%). Therefore, early detection could significantly impact long-term survival.
Currently, cancer antigen 125 (CA-125) is the most widely used serum biomarker for ovarian cancer. Serum concentrations of CA-125 are elevated (>35 U/ml) in 75-80% of patients with advanced-stage disease and this marker is routinely used to follow response to treatment and disease progression in patients from whom CA-125-secreting tumors have been resected. However, because the levels of CA-125 are correlated with tumor volume, only 50% of patients with early-stage disease have elevated levels, indicating that the sensitivity of CA-125 as a screening tool for early stage disease is limited. The utility of CA-125 screening is further limited by the high frequency of false-positive results associated with a variety of benign conditions, including endometriosis, pregnancy, menstruation, pelvic inflammatory disease, peritonitis, pancreatitis, and liver disease. Hence, there has long been a need for a means of detecting ovarian cancer at an early stage and for an ovarian cancer monitoring supplemental to CA-125.